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The biological properties of the optical isomers of propranolol and their effects on cardiac arrhythmias
Author(s) -
BARRETT A. M.,
CULLUM VALERIE A.
Publication year - 1968
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1968.tb07949.x
Subject(s) - propranolol , chronotropic , ouabain , isoprenaline , potency , procaine , chemistry , inotrope , medicine , pharmacology , tachycardia , quinidine , endocrinology , heart rate , blood pressure , sodium , biochemistry , organic chemistry , stimulation , in vitro
1 The optical isomers of propranolol have been compared for their β‐blocking and antiarrhythmic activities. 2 In blocking the positive inotropic and chronotropic responses to isoprenaline, (+)‐propranolol had less than one hundredth the potency of (–)‐propranolol. At dose levels of (+)‐propranolol which attenuated the responses to isoprenaline, there was a significant prolongation of the PR interval of the electrocardiogram. 3 The metabolic responses to isoprenaline in dogs (an increase in circulating glucose, lactate and free fatty acids) were all blocked by (–)‐propranolol. (+)‐Propranolol had no effect on fatty acid mobilization but significantly reduced the increments in both lactate and glucose. 4 Both isomers of propranolol possessed similar depressant potency on isolated atrial muscle taken from guinea‐pigs. 5 The isomers of propranolol exhibited similar local anaesthetic potencies on an isolated frog nerve preparation at a level approximately three times that of procaine. The racemic compound was significantly less potent than either isomer. 6 Both isomers of propranolol were capable of preventing adrenaline‐induced cardiac arrhythmias in cats anaesthetized with halothane, but the mean dose of (–)‐propranolol was 0.09 ± 0.02 mg/kg whereas that of (+)‐propranolol was 4.2 ± 1.2 mg/kg. At the effective dose level of (+)‐propranolol there was a significant prolongation of the PR interval of the electrocardiogram. Blockade of arrhythmias with both isomers was surmountable by increasing the dose of adrenaline. 7 Both isomers of propranolol were also capable of reversing ventricular tachycardia caused by ouabain in anaesthetized cats and dogs. The dose of (–)‐propranolol was significantly smaller than that of (+)‐propranolol in both species but much higher than that required to produce evidence of β‐blockade. 8 The implications of these results are discussed.